Development and Validation of [³H]OF-NB1 for Preclinical Assessment of GluN1/2B Candidate Drugs.

ABSTRACT: GluN2B-enriched N-methyl-D-aspartate receptors (NMDARs) are implicated in several neurodegenerative and psychiatric diseases, such as Alzheimer's disease. No clinically valid GluN1/2B therapeutic exists due to a lack of selective GluN2B imaging tools, and the state-of-the-art [³H]ifenprodil shows poor selectivity in drug screening. To this end, we developed a tritium-labeled form of OF-NB1, a recently reported selective GluN1/2B positron emission tomography imaging (PET) agent, with a molar activity of 1.79 GBq/µmol. The performance of [³H]OF-NB1 and [³H]ifenprodil was compared through head-to-head competitive binding experiments, using the GluN1/2B ligand CP-101,606 and the sigma-1 receptor (σ1R) ligand SA-4503. Contrary to [³H]ifenprodil

SUBMITTER: Ahmed H 

PROVIDER: S-EPMC9416150 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature